Recent investigations have demonstrated that nonenzymatic glycosylation of several proteins, including basement membrane collagen, occurs in patient with diabetes mellitus. It has been suggested that connective tissue complications, such as scleroderma-like skin changes and vascular disease, which are associated with hyperglycemia, may be the consequence of nonenzymatic glucosylation of collagen or elastin; degradation of glycosylated proteins by collagenases or elastases, the rate of fiber formation, or the cross-linking of collagen or elastin molecules may be altered, due to the presence of glucose bound in ketoamine linkage. The specific aims of the investigations proposed here are: 1) to measure the extent of nonenzymatic glucosylation of various collagen types and tropoelastin, by amino acid analyses of glucitol derivatives of [3H]-lysine and [3H]-hydroxylysine, 2) to determine the rates of digestion of various collagen types and elastin, which have been nonenzymatically glucosylated, by collagenases and elastases, and 3) to perform solubility and cross-link analyses of skin collagen from diabetic patients and of aortic collagen and elastin from streptozotocin diabetic rats, by fluorometric analysis of browning (Amadori) reaction products and amino acid analyses of cross-link compounds. Studies carried out in adult diabetic scleredema patients and in children with diabetic scleroderma-like skin changes will attempt to correlate biochemical alterations with hemoglobin AIc levels and existence of other complications. For studies of rat aortae, biochemical findings will be correlated to measurements of tensile strength of aortic rings. Thus, the intent of this investigation is to understand the functional significance of nonenzymatic glycosylation of the two major connective tissue proteins, collagen and elastin. Once the functional aberrations associated with nonenzymatic glucosylation are delineated, we will better understand the pathogenesis of diabetic complications, in addition to broadening our knowledge of collagen and elastin biochemistry in general.